Redundancy of autocrine loops in human osteosarcoma cells

Int J Cancer. 1999 Feb 9;80(4):581-8. doi: 10.1002/(sici)1097-0215(19990209)80:4<581::aid-ijc16>;2-o.


With the aim of identifying innovative therapeutic strategies for osteosarcoma patients who are refractory to conventional chemotherapy, we analyzed the in vitro effects of the blockage of autocrine circuits. Since the insulin-like growth factor-I receptor (IGF-IR)-mediated loop is relevant to the growth of osteosarcoma, we analyzed the activity of the IGF-IR-blocking antibody alphaIR3 in both sensitive and multidrug-resistant osteosarcoma cell lines. Only limited effects, however, were observed, suggesting the simultaneous existence of other autocrine circuits. Indeed, in a representative panel of 12 human osteosarcoma cell lines, in addition to the IGF-IR-mediated circuit, we demonstrated also a loop mediated by epidermal growth factor receptor as well as the presence of nerve growth factor, low-affinity nerve growth factor receptor as well as tyrosine receptor kinase A in the great majority of osteosarcomas. Therapies based on the inhibition of single circuits may have only limited effects in osteosarcoma, whereas the use of suramin, a drug which, besides other activities, non-selectively interferes with the binding of growth factors to their receptors, appears as a promising alternative, in both sensitive and drug-resistant osteosarcoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Autocrine Communication / drug effects
  • Autocrine Communication / physiology*
  • Becaplermin
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / metabolism*
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Epidermal Growth Factor / metabolism
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor II / metabolism
  • Neoplasm Proteins / metabolism*
  • Nerve Growth Factors / metabolism
  • Osteosarcoma / drug therapy
  • Osteosarcoma / metabolism*
  • Platelet-Derived Growth Factor / metabolism
  • Proto-Oncogene Proteins c-sis
  • Receptor, IGF Type 1 / metabolism
  • Receptors, Growth Factor / metabolism*
  • Suramin / pharmacology
  • Transforming Growth Factor alpha / metabolism
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Neoplasm Proteins
  • Nerve Growth Factors
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • Receptors, Growth Factor
  • Transforming Growth Factor alpha
  • Becaplermin
  • Suramin
  • Epidermal Growth Factor
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Receptor, IGF Type 1